Pentosan polysulfate maculopathy: clinical considerations, pathobiology, and causality

Area of Science:

• Ophthalmology
• Toxicology
• Pharmacology

Background:

• Pentosan polysulfate (PPS) is prescribed for interstitial cystitis/bladder pain syndrome.
• Prolonged PPS use is linked to a progressive, vision-threatening retinal disorder.
• This condition, PPS maculopathy, causes impaired dark adaptation and central vision loss.

Purpose of the Study:

• To review the clinical characteristics and public health impact of PPS maculopathy.
• To explore potential pathogenic mechanisms of PPS-induced retinal toxicity.
• To present evidence supporting a causal link between PPS use and macular pathology.

Main Methods:

• Review of clinical, laboratory, and epidemiological evidence.
• Analysis of fundus imaging findings (hyperpigmented macular clumps, autofluorescence abnormalities).
• Evaluation of dose-response relationships and confounding factors.

Main Results:

• PPS maculopathy presents with characteristic fundus abnormalities.
• The condition can progress even after PPS cessation, potentially leading to macular atrophy.
• Evidence supports a biologically plausible mechanism of direct RPE/choroid toxicity.

Conclusions:

• A strong causal relationship exists between PPS use and maculopathy.
• Tens of thousands are at risk due to widespread PPS use and rising prescriptions.
• Increased recognition and understanding of PPS toxicity are urgently needed, especially with new drug applications.